Supplementary Table S1. Concordance of PD-L1 IHC scores for the two cores

Core A / Core B
TC/IC / 0 / 1+ / 2+ / 3+ / Total
0 / 376/188 / 26/80 / 4/2 / 1/0 / 407/270
1+ / 25/74 / 16/124 / 4/6 / 3/0 / 48/204
2+ / 7/0 / 5/5 / 3/6 / 2/0 / 17/11
3+ / 3/0 / 0/2 / 2/0 / 10/0 / 15/2
Total / 411/262 / 47/211 / 13/14 / 16/0 / 487

PD-L1, programmed death-ligand 1; IHC, immunohistochemistry; TC, tumor cells; IC, tumor-infiltrating immune cells

Supplementary Table S2. MMR protein expression

All (N = 487) / %
MLH1 loss / 25 / 5.1
MSH2 loss / 0 / 0
PMS2 loss / 19 / 3.9
MSH6 loss / 0 / 0
MLH1 loss/PMS2 loss / 19 / 3.9
MLH1 loss only / 6 / 1.2

MMR, mismatch repair

Supplementary Table S3. Univariate and multivariate analysis of overall survival

Variables / Univariate analysis / Multivariate analysis
HR (95% CI) / P value / HR (95% CI) / P value
Age / 65 / reference / - / reference / -
≥ 65 / 1.57 (1.16-2.11) / 0.003 / 1.39 (1.01-1.91) / 0.041
Histology / Differentiated / reference / - / reference / -
undifferentiated / 1.35 (1.00-1.81) / 0.051 / 1.48 (1.08-2.03) / 0.014
Depth of invasion / pT1-3 / reference / - / reference / -
pT4 / 1.56 (1.16-2.10) / 0.003 / 1.56 (1.14-2.15) / 0.006
Lymphatic invasion / Absent / reference / - / reference / -
Present / 1.57 (0.87-2.82) / 0.131 / 2.15 (1.16-3.97) / 0.015
Venous invasion / Absent / reference / - / reference / -
Present / 1.49 (0.92-2.40) / 0.102 / 1.47 (0.89-2.43) / 0.131
TNM Stage / III / reference / - / reference / -
IV / 2.24 (1.50-3.35) / 0.001 / 1.934 (1.26-2.97) / 0.003
Adjuvant chemotherapy / No / reference / - / reference / -
Yes / 0.53 (0.40-0.71) / 0.001 / 0.48 (0.36-0.66) / 0.001
PD-L1 in TC / Negative / reference / - / reference / -
Positive / 0.88 (0.62-1.25) / 0.478 / 1.05 (0.68-1.61) / 0.836
PD-L1 in IC / Negative / reference / - / reference / -
Positive / 0.82 (0.61-1.10) / 0.184 / 1.03 (0.72-1.47) / 0.887
CD3 / Low / reference / - / reference / -
High / 0.69 (0.51-0.92) / 0.013 / 1.06 (0.62-1.84) / 0.821
CD4 / Low / reference / - / reference / -
High / 0.77 (0.57-1.03) / 0.075 / 0.91 (0.62-1.32) / 0.606
CD8 / Low / reference / - / reference / -
High / 0.62 (0.46-0.83) / 0.001 / 0.63 (0.39-0.99) / 0.050
FOXP3 / Low / reference / - / reference / -
High / 0.68 (0.51-0.91) / 0.010 / 0.83 (0.58-1.12) / 0.317
MMR / Proficient / reference / - / reference / -
Deficient / 0.85 (0.43-0.67) / 0.635 / 0.66 (0.32-1.37) / 0.265
EBV / Negative / reference / - / reference / -
Positive / 0.76 (0.39-1.50) / 0.424 / 0.89 (0.44-1.61) / 0.748

PD-L1, programmed death-ligand 1; TC, tumor cells; IC, tumor-infiltrating immune cells; MMR, mismatch repair; EBV, Epstein-Barr virus

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